Tipifarnib in Treating Young Patients With Refractory Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00022451
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : March 15, 2012
National Cancer Institute (NCI)
Children's Oncology Group
Information provided by:
National Institutes of Health Clinical Center (CC)

August 10, 2001
January 27, 2003
March 15, 2012
June 2001
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Complete list of historical versions of study NCT00022451 on Archive Site
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Tipifarnib in Treating Young Patients With Refractory Leukemia
A Phase I Trial and Pharmacokinetic Study of R115777 in Pediatric Patients With Refractory Leukemia

RATIONALE: Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase I trial to study the effectiveness of tipifarnib in treating young patients who have refractory leukemia.



  • Determine the maximum tolerated dose and toxicity profile of tipifarnib in pediatric patients with refractory leukemia.
  • Determine the pharmacokinetics of this drug in these patients.
  • Determine the toxicity profile of this drug in these patients.


  • Analyze the gene expression profile of leukemic blasts from these patients before and after treatment with this drug.
  • Determine circulating levels of nerve growth factor and correlate these levels with clinical neurotoxicity from this drug in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive oral tipifarnib every 12 hours on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. At least 9 additional patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 12-34 patients will be accrued for this study within 1-2 years.

Phase 1
Masking: None (Open Label)
Primary Purpose: Treatment
Drug: tipifarnib
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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March 2005
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  • Histologically confirmed acute lymphoblastic leukemia, acute nonlymphoblastic leukemia, juvenile myelomonocytic leukemia (JMML), or chronic myelogenous leukemia (CML) in blast crisis

    • Refractory to standard curative therapy
    • Acute promyelocytic leukemia refractory to tretinoin and arsenic trioxide
    • Philadelphia chromosome-positive CML refractory to imatinib mesylate
  • Greater than 25% blasts in bone marrow (M3 bone marrow) except for patients with JMML
  • Active extramedullary disease allowed
  • No active leptomeningeal leukemia



  • 21 and under

Performance status:

  • Karnofsky 50-100% (over 10 years of age)
  • Lansky 50-100% (10 years of age and under)

Life expectancy:

  • Not specified


  • Not required to be normal


  • Bilirubin normal
  • SGPT and SGOT normal
  • No significant hepatic dysfunction
  • No grade 3 or 4 liver function test results within the past month


  • Creatinine normal OR
  • Creatinine clearance at least 60 mL/min
  • No significant renal dysfunction


  • No significant cardiac dysfunction


  • No significant pulmonary dysfunction


  • No history of grand mal seizures grade 3 or greater except febrile seizures
  • No persistent sensory or motor neuropathy greater than grade 2


  • No clinically significant unrelated systemic illness
  • No serious infection
  • No organ dysfunction that would preclude study participation
  • No requirement for total parenteral nutrition
  • No known allergy to azoles (e.g., clotrimazole, fluconazole, ketoconazole, voriconazole)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception


Biologic therapy:

  • At least 1 week since prior colony-stimulating factor therapy (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) except epoetin alfa
  • At least 3 months since prior myeloablative therapy followed by bone marrow or stem cell transplantation
  • No concurrent immunotherapy
  • No concurrent GM-CSF or interleukin-11


  • At least 2 weeks since prior chemotherapy
  • No concurrent intrathecal chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy:

  • At least 1 week since prior corticosteroids
  • No concurrent corticosteroids (except for acute allergic reaction)


  • At least 4 weeks since prior radiotherapy
  • No concurrent radiotherapy


  • Not specified


  • Recovered from nonhematologic toxicity of all prior therapy
  • At least 1 week since prior retinoids
  • No antacids (magnesium- or aluminum-containing formulations) within 2 hours of study drug
  • No other concurrent investigational agents
  • No concurrent retinoids
  • No concurrent anticonvulsants
Sexes Eligible for Study: All
up to 21 Years   (Child, Adult)
Contact information is only displayed when the study is recruiting subjects
Australia,   Canada,   United States
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National Institutes of Health Clinical Center (CC)
  • National Cancer Institute (NCI)
  • Children's Oncology Group
Study Chair: Brigitte C. Widemann, MD National Cancer Institute (NCI)
National Institutes of Health Clinical Center (CC)
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP